What is the management approach for a patient with IgA (Immunoglobulin A) nephropathy?

Management of IGA Nephropathy

All patients with IgA nephropathy should begin with optimized supportive care including RAS blockade (ACE inhibitors or ARBs) for proteinuria >0.5 g/day regardless of blood pressure, strict BP control to 125/75 mmHg, and comprehensive lifestyle modifications—this forms the foundation of treatment before considering any immunosuppression. 1, 2

Initial Assessment and Risk Stratification

• Obtain kidney biopsy with MEST-C scoring (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and crescents) to assess histologic severity 1, 2
• Use the International IgAN Prediction Tool (available at Calculate by QxMD) to estimate prognosis, though recognize this cannot predict treatment response 1, 2
• Identify high-risk features: proteinuria >1 g/day, hypertension, reduced eGFR at presentation, and adverse MEST-C findings 2, 3
• Proteinuria is the single most important clinical predictor of outcome, with persistent proteinuria >1 g/day conferring significant risk of GFR loss and progression to kidney failure 3

First-Line Treatment: Optimized Supportive Care (All Patients)

RAS Blockade

• Initiate ACE inhibitors or ARBs for all patients with proteinuria >0.5 g/day, even if normotensive (Grade 1B recommendation) 1, 2
• Titrate to maximally tolerated doses to achieve proteinuria reduction 1
• Target blood pressure of 125/75 mmHg or lower 4

Lifestyle and Cardiovascular Risk Management

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) 2
• Achieve and maintain desirable body weight 5
• Implement smoking cessation 5
• Encourage regular exercise program 5
• Consider statin therapy for any proteinuria >0.5 g/day due to cardiovascular risk 3
• Maintain high fluid intake and avoid nephrotoxin exposure 5

Additional Supportive Measures

• Administer pneumococcal and influenza vaccines 2
• For patients with declining renal function, initiate low protein/low phosphate diet with phosphate binders early 5

Treatment Duration Before Escalation

• Continue optimized supportive care for at least 90 days (3 months) before considering immunosuppression 1, 2
• Target proteinuria reduction to <1 g/day, which is associated with favorable prognosis regardless of initial level 3

Immunosuppression for High-Risk Progressive Disease

When to Consider Immunosuppression

Consider glucocorticoids or clinical trial enrollment only if proteinuria remains >0.75-1 g/day after at least 90 days of optimized supportive care AND eGFR ≥30 mL/min/1.73 m² 1, 2

Glucocorticoid Therapy (Grade 2B)

• Consider 6-month course of systemic glucocorticoids for eligible high-risk patients 1, 2

• Exercise extreme caution or avoid glucocorticoids entirely in patients with: 1

  • eGFR <30 mL/min/1.73 m² (adverse effects more likely with eGFR <50) 1
  • Diabetes mellitus 1
  • Obesity (BMI >30 kg/m²) 1
  • Advanced age 1
  • Metabolic syndrome 1
  • Latent infections (tuberculosis, hepatitis B/C, HIV) 1
  • Active peptic ulceration 1
  • Uncontrolled psychiatric disease 1
  • Severe osteoporosis 1

• Conduct detailed risk-benefit discussion with each patient before initiating glucocorticoids, as clinical benefit is not definitively established and infectious complications can be severe 1, 6

Population-Specific Considerations

• Chinese patients only: Mycophenolate mofetil may be used as a glucocorticoid-sparing agent 1, 2
• Japanese patients only: Consider tonsillectomy 1, 2
• Non-Chinese and non-Japanese patients: These interventions are not recommended 1

Immunosuppressive Agents NOT Recommended

• Do not use azathioprine, cyclophosphamide (except rapidly progressive disease), calcineurin inhibitors, or rituximab for standard IgAN treatment 1, 2

Special Clinical Situations

Rapidly Progressive IgAN with Crescentic Disease

• For patients with extensive crescent formation (>50% of glomeruli) and declining GFR, treat with cyclophosphamide and glucocorticoids following ANCA-associated vasculitis protocols 1, 2
• Note that crescents without GFR decline do not constitute rapidly progressive disease, but require close monitoring 1

IgAN with Minimal Change Disease Features

• Treat according to minimal change disease guidelines (Chapter 5 of KDIGO) if biopsy shows mesangial IgA deposition with otherwise minimal change histology 1

IgAN with Acute Kidney Injury

• For AKI from severe visible hematuria, provide supportive care for AKI 1
• Consider repeat kidney biopsy if no improvement within 2 weeks after hematuria cessation 1

Nephrotic-Range Proteinuria

• Evaluate for coexistent secondary FSGS (from obesity, uncontrolled hypertension) or extensive glomerulosclerosis with tubulointerstitial fibrosis 1
• Manage as high-risk IgAN if mesangioproliferative features are present 1

Emerging Therapies Under Investigation

Strongly consider enrollment in clinical trials when available, as multiple promising therapies are being evaluated 1, 2

Agents Augmenting Supportive Care

• SGLT2 inhibitors (showing promise across proteinuric kidney diseases) 1, 7
• Sparsentan and atrasentan (endothelin blockade) 1, 7
• Hydroxychloroquine 1

Disease-Specific Targeted Therapies

• Enteric-coated budesonide (targeting gut-associated lymphoid tissue) 1, 6
• Complement inhibitors 1, 6, 7
• B-cell targeted therapies (BAFF blockade) 6, 7

Monitoring and Treatment Targets

• Target proteinuria reduction to <1 g/day as a surrogate marker of improved kidney outcome 1, 2
• Monitor for reduction in slope of GFR decline as favorable outcome 2
• A 40% or greater decline in eGFR from baseline over 2-3 years indicates poor outcome 2
• Offer participation in disease registries when available 1, 2

Critical Pitfalls to Avoid

• Do not initiate immunosuppression without first completing at least 90 days of optimized supportive care with maximally tolerated RAS blockade 1, 2
• Do not use glucocorticoids in patients with eGFR <30 mL/min/1.73 m² or multiple risk factors for toxicity, as adverse events significantly increase 1
• Do not apply mycophenolate mofetil or tonsillectomy recommendations outside their specific ethnic populations (Chinese and Japanese, respectively) 1, 2
• Do not use cyclophosphamide, azathioprine, calcineurin inhibitors, or rituximab for standard IgAN—reserve cyclophosphamide only for true rapidly progressive crescentic disease 1, 2